Rebamipide nanocrystal with improved physicomechanical properties and its assessment through bio-mimicking 3D intestinal permeability model.

This study investigated the formulation and characterization of rebamipide nanocrystals (REB-NCs) to enhance the solubility and permeability of rebamipide, an anti-ulcer medication known for its low aqueous solubility and permeability, classified as BCS class IV. Employing high-pressure homogenization and wet milling techniques, we successfully achieved nanonization of rebamipide, resulting in stable nanosuspensions that were subsequently freeze-dried to produce REB-NCs with an average particle size of 223 nm. Comprehensive characterization techniques, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) confirmed the crystalline nature of the nanocrystals and their compatibility with the selected excipients.

Comprehensive Study on Solomonamides: Total Synthesis, Stereochemical Revision, and SAR Studies toward Identification of Simplified Lead.

Solomonamides, a pair of macrocyclic peptide natural products originating from marine sources, have garnered significant attention within the synthetic community owing to their marked anti-inflammatory efficacy and intricate molecular architectures. In this paper, we present a very detailed investigation into solomonamides, including the challenges associated with the total synthesis, the evolution of our synthetic strategies, structural reassignment, synthesis of all possible stereoisomeric macrocycles, biological assessment, structure-activity relationship (SAR) studies, etc. Within the ambit of this total synthesis, diverse strategies for macrocyclization were rigorously explored, encompassing the Friedel-Crafts acylation, cyclization involving the aniline NH moiety, macrolactamization utilizing Gly-NH, and Heck macrocyclization methodologies.

Application of Vinamidinium Salt Chemistry for a Palladium Free Synthesis of Anti-Malarial MMV048: A "Bottom-Up" Approach.

MMV390048 () is a clinical compound under investigation for antimalarial activity. A new synthetic route was developed which couples two aromatic fragments while forming the central pyridine ring over two steps. This sequence takes advantage of raw materials used in the existing etoricoxib supply chain and eliminates the need for palladium catalysts, which were projected to be major cost-drivers.

Physics-informed machine learning: case studies for weather and climate modelling.

Machine learning (ML) provides novel and powerful ways of accurately and efficiently recognizing complex patterns, emulating nonlinear dynamics, and predicting the spatio-temporal evolution of weather and climate processes. Off-the-shelf ML models, however, do not necessarily obey the fundamental governing laws of physical systems, nor do they generalize well to scenarios on which they have not been trained. We survey systematic approaches to incorporating physics and domain knowledge into ML models and distill these approaches into broad categories.

Synthesis of an Oxathiolane Drug Substance Intermediate Guided by Constraint-Driven Innovation.

A new route was developed for construction of the oxathiolane intermediate used in the synthesis of lamivudine (3TC) and emtricitabine (FTC). We developed the presented route by constraining ourselves to low-cost, widely available starting materials-we refer to this as supply-centered synthesis. Sulfenyl chloride chemistry was used to construct the framework for the oxathiolane from acyclic precursors.

Access to a Stereoisomer Library of Solomonamide Macrocycles.

In an attempt towards understanding stereo-structure activity relationships (SSARs), we have prepared eight possible stereoisomers of solomonamide macrocycles, in particular, by changing the stereochemical pattern of non-peptide fragment AHMOA. Here, we have demonstrated different ways to construct three contiguous chiral centers present in solomonamide B macrocycle using substrate/reagent-controlled methods. These methods involve Brown crotylation, NHK reaction and Evans aldol addition as key steps to synthesize key non-peptide fragment.

An innovative modified feeding appliance for an infant with cleft lip and cleft palate: A case report.

Cleft lip and palate is one of the most common craniofacial anomalies of humans. A child born with cleft lip and palate may experience difficulties while feeding due to lack of seal of the oral cavity due to incomplete facial and palatal structures. Difficulty in feeding leads to inadequate nutrition and affects the health of the infant.

Discovery of Potent and Selective A Antagonists with Efficacy in Animal Models of Parkinson's Disease and Depression.

Adenosine A receptor (AAdoR) antagonism is a nondopaminergic approach to Parkinson's disease treatment that is under development. Earlier we had reported the therapeutic potential of 7-methoxy-4-morpholino-benzothiazole derivatives as AAdoR antagonists. We herein described a novel series of [1,2,4]triazolo[5,1-]purin-2-one derivatives that displays functional antagonism of the A receptor with a high degree of selectivity over A, A, and A receptors.

Total Synthesis of the Marine Natural Product Solomonamide B Necessitates Stereochemical Revision.

The first total synthesis of the proposed structure of solomonamide B has been achieved. However, the (1)H and (13)C NMR spectral data of the synthesized compound was not exactly matching with that of the natural solomonamide B. This prompted us to revise the originally proposed structure, in particular, the stereochemistry of the nonpeptide part, which was confirmed by its total synthesis.

Enhancing the Dental Professional's Responsiveness Towards Domestic Violence; A Cross-Sectional Study.

Background: Dentists may be the first health care professionals to treat patients who have experienced Oro-facial trauma resulting from Domestic violence (DV). Hence, as a national health concern, it challenges the social responsibility of a dentist in bringing down its prevalence.

Objective: To assess the knowledge of Domestic violence among dentists of Karnataka.

Breaking and making of olefins simultaneously using ozonolysis: application to the synthesis of useful building blocks and macrocyclic core of solomonamides.

A simple and practical one-pot, two-directional approach to access olefinic esters through simultaneous breaking and making of olefins using ozonolysis of alkenyl aryl selenides is disclosed. The scope of the method with a variety of examples is demonstrated, and the end products obtained here are useful building blocks. As a direct application of the present method, the macrocyclic core of potent anti-inflammatory natural cyclic peptides, solomonamides, is synthesized.

Labial ankyloglossia associated with oligodontia: a case report.

Developmental disturbances of the tongue (aglossia, macroglossia, microglossia, and ankyloglossia) can adversely affect the development of the surrounding structures including the palate, alveolar process, and teeth. These developmental disturbances impair functions such as mastication, speech, and swallowing. Ankyloglossia is of various types and may be associated with other syndromic features like cleft palate.

One-pot quadruple/triple reaction sequence: a useful tool for the synthesis of natural products.

Multiple reactions in one pot has always been a useful technique for synthetic organic chemists, as it can minimizes solvent usage, time and the number of purification steps when compared to individual multi-step syntheses. In line with this, here in this perspective we discuss a one-pot quadruple/triple reaction sequence comprising an enyne ring-closing metathesis/cross-metathesis/Diels-Alder/aromatization for the synthesis of natural products setting.

Total synthesis of Deoxy-solomonamide B by mimicking biogenesis.

A total synthesis of Deoxy-solomonamide B was accomplished starting from tryptophan in an efficient manner by mimicking the proposed biogenetic route. The present synthesis utilizes a crotylation, oxidative cleavage of the indole moiety, and macrolactamization as key steps. The use of the indole nucleus as a masked anthranilic acid unit paves the way for the easy synthesis of related macrocycles and natural products where the ortho-acyl aniline moiety is embedded into them, which otherwise is difficult to synthesize.

Nosocomial infections in patients admitted in intensive care unit of a tertiary health center, India.

Background: Patients in Intensive Care Units (ICUs) are a significant subgroup of all hospitalized patients, accounting for about a quarter of all hospital infections.

Aim: The aim was to study, the current status of nosocomial infection, rate of infection and distribution of infection among patients admitted in Medical Intensive Care Unit (MICU) of a District Hospital.

Subjects And Methods: Data were collected retrospectively from 130 patient's records presented with symptoms of nosocomial infection in MICU of a Tertiary Health Center, Tumkur from August 2012 to May 2013.

Total synthesis of an anticancer norsesquiterpene alkaloid isolated from the fungus Flammulina velutipes.

The first total synthesis of a norsesquiterpene alkaloid (R)-8-hydroxy-4,7,7-trimethyl-7,8-dihydrocyclopenta[e]isoindole-1,3(2H,6H)-dione, isolated from the mushroom-forming fungus Flammulina velutipes, in both racemic and enantiomeric pure forms, is reported. The (-)-enantiomer of the natural product has been synthesized from the D-(-)-pantolactone chiral pool. The synthesis features a one-pot, three-step reaction sequence comprising an enyne RCM/Diels-Alder/aromatization to construct the desired indane skeleton present in the natural product.

Studies toward the synthesis of potent anti-inflammatory peptides solomonamides A and B: synthesis of a macrocyclic skeleton and key fragment 4-amino-6-(2'-amino-4'-hydroxyphenyl)-3-hydroxy-2-methyl-6-oxohexanoic acid (AHMOA).

A first synthetic effort toward total synthesis of highly potent solomonamides is disclosed. An efficient strategy to synthesize this class of compounds, along with the synthesis of a core macrocycle (shown in red) and the key fragment AHMOA, is described.

Diet and nutritional status of rural preschool children in Punjab.

Objective: To assess diet and nutritional profile of rural preschool children of Punjab.

Study Design: Multistage random sampling method was adopted by following probability proportion to population size (PPS).

Subject: Four hundred households (HH) were covered in each district of Punjab for socio-economic and demographic information.